The goal of this research is to improve our understanding of respiratory, metabolic and cardiovascular control during exercise and to elucidate the mechanisms by which disease limit work performance. Computerized data analyses are used to yield descriptions of physiological responses to exercise and underlying mechanisms. While exercise is the principal cardiorespiratory stress in life, there is a general failure to appreciate the mechanisms which drive ventilation during exercise and cause exertional dyspnea. However, evidence is accumulating in our laboratory which suggests that exercise hyperpnea is closely coupled to CO2 delivery to the lung. This would imply that the chemical controller functions to keep arterial PCO2 relatively fixed by stimulating ventilation proportional to CO2 delivery to the lung. These data also suggest that chemical control overrides other mechanisms responsive to breathing stimuli. We propose to test this hypothesis during: 1) onset, 2) transition to steady-state, and 3) steady-state of exercise while perturbing certain physiological factors. We propose to study effects of limiting the rate of cardiac output increase, altering the CO2 set-point, attenuating the carotid bodies with 100 percent O2, varying CO2 output by diet, and continuously varying dead space on ventilation. Responses will be studied below and above the anaerobic threshold to discern the effects of superimposed metabolic acidosis. An additional thrust is to study factors affecting gas exchange during exercise. A single exercise test to measure anaerobic threshold, maximal 02 uptake, work efficiency and the time constant of 02 uptake kinetics has been developed and is being used to evaluate the alterations in gas exchange. The pathophysiological processes which alter breathing patterns is being studied in order to define the usefulness of these measurements in the differential diagnosis of patients limited in the performance of exercise.